PROJECT SUMMARY While optogenetics is well-suited for ?understanding the dynamic activity of neural circuits? ? the first central theme of the NIH BRAIN Initiative (PAR-15-090), its neurochemical impacts remain largely uncharacterized due to a lack of appropriate tools. Given that the predominant mode of cellular interactions is neurochemical, commercial development of such tools will fulfill the goals set by the first as well as the second central theme of the NIH BRAIN Initiative ? ?developing novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function.? This R41 project aims to fulfill these goals through Aim 1 ? prototype development and Aim 2 ? prototype validation of a unified system for wireless optogenetics and brain microdialysis for small molecules (including but not limited to glutamate, dopamine, GABA, serotonin, norepinephrine and acetylcholine). Brain microdialysis is a well-established method capable of comprehensive as well as high-throughput (?multiplex?) neurochemical profiling. Microdialysis supports a wide range of application (neurochemical targets) as well as a high level of efficiency, sensitivity, accuracy, practicality, maintainability, and manufacturability. The proposed unified system of wireless optogenetics and brain microdialysis is expected to possess high research as well as business potentials and help address unexplored questions in neuroscience ? that cannot be adequately addressed by the current technologies. The prototype development (design and production) will be based on existing products from Eicom-USA. By taking advantage of our own market tested technologies, we attempt to maximize the technical feasibility, minimize the R&D challenge, and thus attain both high product development feasibility and high benefit-cost ratio (BCR) while reducing the ?time to market (TTM)?. Two systems ? one ?main? and the other ?backup? (for potential pitfalls) ? are proposed. The prototype validation (?iterate refinement?) will be achieved ? as specified by NIH ? through ?feedback from end-users in the context of the intended experimental use? ? thus ensuring ?reliable, broad, sustainable dissemination and incorporation of the final products into regular neuroscience practice.? For this premise, the prototypes will be utilized for ?afferent (neuronal input)-specific neurochemical profiling? in freely moving animals to address an unexplored question in neuroscience. First, the expected results will validate the prototypes. Second, the results will also serve as the first direct evidence comprehensively characterizing the neurochemical impacts of optogenetics, establishing the ?proof of concept? as well as ?research benefits? of the proposed system, and thereby providing the ?marketing tools? for the planned commercialization of the final product.